Proton magnetic resonance spectroscopic imaging (1H-MRSI) offers a non-invasive method for the identification, visualization, and quantification of specific brain biochemical markers and neurotransmitters, the assessment of abnormalities in injured or diseased brain tissue, the longitudinal monitoring of degenerative diseases, and the early evaluation of therapeutic interventions. These unique capabilities enable the direct in vivo assessment of the neurochemical status of discrete brain structures with the potential of identifying mechanisms underlying selective brain pathologies. 1H-MRSI has been successful in identifying markers of neuronal health, cell membrane integrity, glial activity, and amino acid neurotransmitter cycling in human studies. Nevertheless, spectroscopic imaging at conventional field strengths suffers from poor spatial resolution, typically on the order of centimeters, and limited spectral resolution, resulting in the robust detection of a relatively small number of metabolites. The clear need to improve sensitivity has been a driving force behind the installation of highfield scanners. This project, written in response to the NIH Program Announcement (PA-06-279): Neurotechnology Research, Development, and Enhancement (R01) - proposes the development of enhanced 1H-MRSI technology needed to exploit the theoretical advantages (enhanced signal-to-noise ratio [SNR], spectral resolution, and information content) available using recently introduced ultrahigh-field 7 Tesla (T) whole-body MR scanners;thus addressing a critical barrier to progress in neurospectroscopy. The goal of this 4-year R01 is to develop optimized 7T 1H-MRSI data acquisition and processing techniques to provide currently unavailable high-spatial resolution and high-SNR biochemical information from selective tissues and small structures throughout the human brain. The successful development of these new imaging tools will have a broad impact on basic science and clinical applications by providing the means to obtain insights into mechanisms of brain health and disease. Applications of these developments include studies of brain development, psychopathology, drug and alcohol dependence, neurodegenerative processes, brain injury, and therapeutic interventions. PUBLIC HEALTH RELEVANCE: Proton magnetic resonance spectroscopic imaging (1H-MRSI) offers a non-invasive method for the identification, visualization, and quantification of specific brain biochemical markers and neurotransmitters, and this project proposes the development of innovative technologies needed to exploit the theoretical advantages offered by recently introduced ultrahigh field 7T human scanners. The goal of this work is to achieve two- to eight-fold higher spatial resolution and coverage, along with the detection of a significantly increased number of metabolites, than possible with existing methods. We anticipate the successful development of these new imaging tools will have a broad impact on basic science and clinical applications by providing the means to obtain insights into mechanisms of brain health and disease, and applications of these developments include studies of brain development, psychopathology, drug and alcohol dependence, neurodegenerative processes, brain injury, and the therapeutic response of focal brain structures.